Clinical outcomes of increased regional amyloid uptake in patients with subthreshold global amyloid levels

Abstract

Background Although the standardized uptake value ratio (SUVR) method is objective and simple, cut‐off optimization using global SUVR values may not reflect focal increased uptake in the cerebrum. The present study investigated clinical and neuroimaging characteristics according to regionally increased β‐amyloid (Aβ) uptake and global Aβ status. Method We recruited 973 patients with Alzheimer's disease ‐related cognitive impairment (ADCI). All patients underwent neuropsychological tests and 501 18F‐florbetaben (FBB) amyloid positron emission tomography (PET) and 472 18F‐flutemetamol (FMM) PET. Each PET scan was assessed in 10 regions (frontal, temporal, parietal, posterior cingulate, and striatum) by regional quantitative SUVR‐based cutoff values for each region using an iterative outlier approach. Result A total of 64 (6.6%) subjects showed increased regional Aβ uptake with subthreshold global Aβ status [focal (+) and global (‐) Aβ group, F(+)G(‐) group]. The F(+)G(‐) group showed worse performance in memory impairment (P < 0.001) and greater hippocampal atrophy (P = 0.024) but not global cognition and cortical thickness, compared to those in the F(‐)G(‐). Participants with diffuse Aβ involvement in the whole region [diffuse (+) and global (+) Aβ group, D(+)G(+)] showed worse neuropsychological (P = 0.008‐0.042) and neuroimaging features (P <0.015) than those with focal Aβ involvement F(+)G(+). Conclusion ] Our findings suggest that individuals show distinctive clinical outcomes according to regionally increased Aβ uptake and global Aβ status. Thus, clinicians should pay more attention to regional increased Aβ uptake in addition to global Aβ status.

Advanced brain imaging for the diagnosis of Alzheimer disease

“…It is important to note that CSF-based Aβ estimates showed up to 10% higher than Aβ-PET-based estimates in people without dementia, suggesting that preclinical and prodromal AD may be more prevalent than previously estimated [44 ▪ ]. In line with this, a study revealed that participants with focally increased amyloid-PET signals, even in subthreshold global Aβ levels, showed AD patterns of neuroimaging and neuropsychological features [45], therefore more attention should be drawn to focal increased Aβ uptake in addition to global Aβ status. As the research criteria for the diagnosis of probable AD have been revised [46], amyloid-PET imaging is getting importance in clinical trials.…”